This invention relates to transgenic animals.
It is possible to insert foreign genes into vertebrate embryos, and for these genes to be incorporated into the genome of the resulting animal. Insertion of the foreign genes has been carried out mechanically (by microinjection), and with the aid of retrovirus vectors (for example, as is described in Huszar et al. (1985) P.N.A.S. U.S.A 82, 8587). The animals resulting from this process are termed xe2x80x9ctransgenic.xe2x80x9d The foreign genes can be sexually transmitted through subsequent generation and are frequently expressed in the animal. In some instances the proteins encoded by the foreign genes are expressed in specific tissues. For example, the metallothionein promoter has been used to direct the expression of the rat growth hormone gene in the liver tissue of transgenic mice (Palmiter et al., 1982 Nature 300;611). Another example is the elastase promoter, which has been shown to direct the expression of foreign genes in the pancreas (Ornitz et al., 1985 Nature 313:600). Developmental control of gene expression has also been achieved in transgenic animals, i-e., the foreign gene is transcribed only during a certain time period, and only in a particular tissue. For example, Magram et al. (1985, Nature 315:338) demonstrated developmental control of gene under the direction of a globin promoter; and Krumlauf et al. (1985, Mol. Cell. Biol. 5:1639) demonstrated similar results using the alpha-feto protein minigene.
In general, the invention features a DNA sequence containing a gene encoding a protein, the gene being under the transcriptional control of a mammalian milk protein promoter which does not naturally control the transcription of the gene, the DNA sequence further including DNA enabling secretion of the protein; e.g., a secretion signal-encoding sequence interposed between the gene and promoter. The promoter can be that of a milk serum protein or a casein protein, although milk serum proteins are preferred, as will be discussed in more detail below. (As used herein, xe2x80x9cgenexe2x80x9d refers to both genomic DNA sequences and cDNA sequences.)
The invention permits the production of any desired protein in an easily maintained stable, portable culture system, i.e., a living domesticated mammal, which is capable not only of producing the desired protein, but preferably of passing on the ability to do so to its female offspring as well. Secretion of the protein into the host mammal""s milk facilitates purification and obviates removal of blood products and culture media additives, some of which can be toxic or carcinogenic. More importantly, protein yields will be high and production will be more cost effective and efficient.
Other features and advantages of the invention will be apparent from the following description of the preferred embodiments thereof, and from the claims.